This amended application seeks support for an interventional study aimed at reducing multi-drug resistance and infections in nursing home (NH) residents. Each year, a staggering 1.5-2.0 million infections occur in NHs. Many of these infections are caused by multiple drug resistant organisms (MDROs) including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and multidrug resistant Gram-negative bacilli (R-GNB). Antimicrobial resistance among common bacteria are adversely affecting the clinical course and exponentially increasing healthcare costs. Recognizing a need for action, legislators, policy makers, and consumer groups are advocating for pathogen-based universal preemptive screening for these MDROs, particularly MRSA in hospitals and NHs. However, implementing this sweeping mandate is controversial, costly, reactive, and not based on empirical evidence. It can result in a 10-20-fold increase in the number of NH residents placed in isolation precautions with the potential for reduced attention by healthcare workers, isolation and functional decline. Our proposal evaluates a novel focused approach between 'do nothing' and 'search all and destroy' strategies by targeting a subgroup of NH residents with indwelling devices who are at a high risk of acquiring MDROs and infections. We hypothesize that our targeted infection control program (TIP) will reduce MDRO colonization and infections in NH residents with indwelling devices. This cluster randomized trial will involve 12 NHs; 6 will be randomized to the TIP arm and 6 to the routine care arm. Our multicomponent TIP intervention will include: Component 1: Institute enhanced barrier precautions for all NH residents with indwelling devices; active screening for MDROs (monthly) using cultures collected from multiple body sites to identify asymptomatic MDRO carriage in these residents; and dissemination of results to clinical staff and administration. Component 2: Structured, active surveillance for infections using standardized definitions in residents with indwelling devices and dissemination of results to clinical staff and administration. Component 3: A hand hygiene promotion program. Component 4: A structured educational program pertaining to indwelling device care for healthcare workers. Our research will determine if our multi-component TIP intervention reduces asymptomatic carriage of MDROs (primary outcome) and symptomatic infections (secondary outcome) in a high-risk sub-group of NH residents with indwelling devices. The proposed research will also provide novel insight into the molecular epidemiology and mechanisms of transmission of resistant pathogens. Using molecular methods, we will determine the genetic relatedness of MDRO between residents with indwelling devices within and between different facilities, trace the source of any new strain, and evaluate the impact of our intervention on specific strains. Our results will allow infection control practitioners, healthcare workers, clinicians, policy makers, legislatures, and consumers to better address antimicrobial resistance and infections in older adults in NHs.